Primary immunodeficiencies unravel critical aspects of the pathophysiology of autoimmunity and of the genetics of autoimmune disease.

Abstract

BACKGROUND:

Primary Immunodeficiencies (PIDs) represent unique opportunities to understand the operation of the human immune system. Accordingly, PIDs associated with autoimmune manifestations provide insights into the pathophysiology of autoimmunity as well as into the genetics of autoimmune diseases (AID). Epidemiological data show that there are PIDs systematically associated with AID, such as immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), Omenn syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS), and C1q deficiency, while strong associations are seen with a handful of other deficits.

CONCLUSION:

We interpret such stringent disease associations, together with a wealth of observations in experimental systems, as indicating first of all that natural tolerance to body components is an active, dominant process involving many of the components that ensure responsiveness, rather than, as previously believed, the result of the mere purge of autoreactivities. More precisely, it seems that deficits of Treg cell development, functions, numbers, and T cell receptor repertoire are among the main factors for autoimmunity pathogenesis in many (if not all) PIDs most frequently presenting with autoimmune features. Clearly, other pathophysiological mechanisms are also involved in autoimmunity, but these seem less critical in the process of self-tolerance. Comparing the clinical picture of IPEX cases with those, much less severe, of ALPS or APECED, provides some assessment of the relative importance of each set of mechanisms.

• Authors: Antonio Coutinho, Magda Carneiro-Sampaio
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 28 Suppl 1 Pg. S4-10 (May 2008) ISSN: 0271-9142 [Print] Netherlands
• PMID: 18293069 (Publication Type: Journal Article, Review)

Chemical References

• DNA-Binding Proteins
• FOXP3 protein, human
• Forkhead Transcription Factors
• Homeodomain Proteins
• Nuclear Proteins
• RAG2 protein, human
• Transcription Factors
• RAG-1 protein
• Complement C1q

Topics

• Animals
• Autoimmune Diseases (complications, genetics, physiopathology)
• Autoimmunity
• Complement C1q (deficiency, genetics)
• DNA-Binding Proteins (deficiency, genetics)
• Forkhead Transcription Factors (genetics, immunology)
• Gene Rearrangement, B-Lymphocyte
• Gene Rearrangement, T-Lymphocyte
• Genetic Predisposition to Disease
• Homeodomain Proteins (genetics)
• Humans
• Immunologic Deficiency Syndromes (complications, genetics, immunology, physiopathology)
• Mice
• Nuclear Proteins (deficiency, genetics)
• Polymorphism, Genetic
• Self Tolerance (genetics)
• Transcription Factors (deficiency, genetics, immunology)
• AIRE Protein